Patched 1 expression in Merkel cell carcinoma

被引:10
作者
Gambichler, Thilo [1 ]
Dreissigacker, Max [1 ]
Kasakovski, Dimitri [1 ]
Skrygan, Marina [1 ]
Wieland, Ulrike [2 ]
Silling, Steffi [2 ]
Gravemeyer, Jan [3 ]
Melior, Anita [3 ]
Cherouny, Angela [3 ]
Stuecker, Markus [1 ]
Stockfleth, Eggert [1 ]
Sand, Michael [1 ]
Becker, Juergen C. [3 ,4 ]
机构
[1] Ruhr Univ Bochum, Skin Canc Ctr, Dept Dermatol, Bochum, Germany
[2] Univ Cologne, Inst Virol, Natl Reference Ctr Papilloma & Polyomaviruses, Cologne, Germany
[3] Univ Duisburg Essen, German Canc Consortium DKTK Partner Site Essen Du, Translat Skin Canc Res, Dept Dermatopathol, Essen, Germany
[4] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany
关键词
Gene expression; Merkel cell carcinoma; Merkel cell polyomavirus; Hedgehog signaling; Patched 1 | Gene expression; PTCH; POLYOMAVIRUS; POLYMORPHISM; MUTATIONS;
D O I
10.1111/1346-8138.15611
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
The relevance of Hedgehog signaling in Merkel cell carcinoma has only been addressed by a few studies with conflicting results. Thus, we aimed to establish the expression of Hedgehog signaling molecules in Merkel cell carcinoma to characterize causes of aberrant expression and to correlate these findings with the clinical course of the patients. Immunohistochemistry was performed for Sonic, Indian, Patched 1 (PTCH1) and Smoothened on patients' tumor tissue. Respective mRNA expression was analyzed in 10 Merkel cell carcinoma cell lines using quantitative real-time polymerase chain reaction. PTCH1 sequencing and DNA methylation microarray analyses were carried out on tumor tissues as well as cell lines. PTCH1 immunoreactivity in Merkel cell carcinoma was similar to that of basal cell carcinomas, which both significantly differed from PTCH1 immunoreactivity in healthy skin. Most PTCH1 mutations found were synonymous or without known functional impact. However, on average, the promoter regions of both PTCH1 were hypomethylated independently from PTCH1 gene expression or Merkel cell polyomavirus status. PTCH1 and GLI1/2/3 genes were differently expressed in different cell lines; notably, there was a significant correlation between GLI2 and PTCH1 mRNA expression. Similar to PTCH1 protein expression in patient tissues, PTCH1 gene expression in Merkel cell carcinoma cell lines is highly variable, but due to the similar methylation pattern across Merkel cell carcinoma cell lines, effects other than methylation seem to be the reason for the differential expression and PTCH1 appears to be upregulated by GLI as a classical Hedgehog target gene.
引用
收藏
页码:64 / 74
页数:11
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